Efficacy of Plasmapheresis in Patients of Drug-Induced Liver Injury (DILI) With Underlying Chronic Liver Disease

Efficacy of Plasmapheresis in Patients of Drug-Induced Liver Injury (DILI) With Underlying Chronic Liver Disease: An Open Labelled RCT

DILI is an underdiagnosed and under appreciated causal or contributing factor to liver injury. DILI can mimics features of the entire spectrum of acute and chronic liver disease.

Asia-Pacifc region is characterized by two unique features; the high prevalence of tuberculosis (TB) in the population and the ubiquitous use of traditional and complimentary medicines.Current definition of Hy's law presents significant difficulties when dealing with patients with preexisting CLD in clinical trials. Hallmark of the hepatic manifestation in these patients is hyperbilirubinemia and coagulopathy rather than ALT elevation.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Liver Disease; Drug Induced Liver Injury
• Intervention / Treatment: Biological: High volume Plasma Exchange; Other: Standard Medical Treatment

Detailed Description

Study Design Single-center, non-blinded, parallel group, randomized controlled trial. Allocation ratio between two groups: 1:1.

Study population: Adults aged 18-75 years with previously known or unknown underlying CLD Diagnosis of DILI-based causality of assessment by RECAM. Severe DILI with bilirubin > 12mg/dl or INR>2, S.Bili >5 mg/dl Consent to participate in the study (based on biopsy, imaging or clinical criteria).

Study design: RCT Study period: 1 year Sample size: 96 Intervention: Patients after screening for all exclusion criteria will be randomized into either the standard treatment group or the plasma exchange group.

Monitoring and assessment: All patients would undergo vital and baseline parameter screening before randomization. Based on randomization they will receive either steroid or plasma exchange followed by steroid.

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Dr Shasthry SM, DM; Phone Number: 01146300000; Email: shasthry@gmail.com
• Study Contact Backup: Name: Dr Khushboo Yadav, MD; Phone Number: 01146300000; Email: ky29277@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences (ILBS)
      • Contact: Dr Khushboo Yadav, MD; Phone Number: 01146300000; Email: ky29277@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults aged 18-75 years with previously known or unknown underlying CLD.
2. Diagnosis of DILI based causality of assessment by RECAM.
3. Severe DILI with bilirubin > 12mg/dl or INR>2, S.Bili >5 mg/dl.
4. Consent to participate in the study (based on biopsy/imaging/or clinical criteria).

Exclusion Criteria:

1. Active infection
2. Contraindications to plasmapheresis (e.g., severe coagulopathy, hemodynamic instability, patients with sepsis, shock, poor P/F ratio).
3. Pregnant or breastfeeding women.
4. HCC or any malignancy
5. UGI bleed, uncontrolled HE
6. Option LTx being considered
7. S. Creatinine > 2mg/dL
8. DILI ALF
9. Alcoholic Hepatitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PLEX with SMT; High Volume Plex with minimum 3 sessions on alternate days along with Standard treatment.	Biological: High volume Plasma Exchange; High volume Plasma Exchange with minimum 3 sessions on alternate days; Other: Standard Medical Treatment; Standard Medical Treatment includes stopping the offending drug,nutrition,injection NAC,Tablet UDCA,steroid in DILI AIH
Active Comparator: Standard Medical Treatment; Standard treatment.	Other: Standard Medical Treatment; Standard Medical Treatment includes stopping the offending drug,nutrition,injection NAC,Tablet UDCA,steroid in DILI AIH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Liver Transplant free survival at the end of 30 days between two groups.	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in arterial lactate levels, on lactate clearance at 0, 3, 5 days	0, 3, 5 days
Reduction in von Willebrand factor levels, endothelial function, and coagulopathy at 0 and 30 day.	0 and 30 day.
Changes in the inflammatory milieu, IL6, IL10, and TNF alpha at 0 and 30 day.	0 and 30 day.
Change in liver-related decompensation events (ascites, HE, variceal bleed) at 0, 3, 5,30, and 90 days.	0, 3, 5,30, and 90 days.
Change in serum bilirubin and bile acids clearance at 0, 3, 5,30 and 90 days.	0, 3, 5,30 and 90 days.

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Estimated): January 25, 2025
• Primary Completion (Estimated): January 31, 2026
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: January 22, 2025
• First Submitted That Met QC Criteria: January 27, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 27, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Poisoning; Wounds and Injuries; Liver Diseases; Chemical and Drug Induced Liver Injury
• Other Study ID Numbers: ILBS-DILI-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No